Changes in the dietary content of fat, starch and protein result in adaptive changes in the synthesis and activity of the pancreatic digestive enzymes: lipase, amylase, trypsinogen, and chymotrypsinogen. The mechanisms of these adaptations are unknown, but represent important examples of nutrient interaction in the regulation of gene expression and translation. Understanding these mechanisms is important for advancing our knowledge of nutrient regulation of cellular functions. The mechanisms of adaptation of pancreatic lipase and amylase will be studied in vitro in primary, serum-free cultures of acinar cells. The possible coordinated, but opposing, regulation of these enzymes will be evaluated. The role of glucose, and its interaction with insulin and gastrointestinal hormones, in the regulation of both enzymes will be investigated. The effects of fatty acids, their saturation, and their chain length on the regulation of both enzymes will be examined in cultured acinar cells. The possible role of ketones in this regulation will be examined. The interaction of glucose, insulin, ketones, fatty acids, and cholecystokinin will be examined in the regulation of both enzymes. The effects of these nutrients and metabolites on cellular DNA, protein, amylase and lipase will be measured. The rates of synthesis of amylase and lipase will also be measured by labeled amino acid incorporation. Cellular glucose utilization (uptake and oxidation) as well as fatty acid and ketone oxidation will be determined. To determine if regulatory agents identified in these studies act by altering gene expression, the mRNA coding for amylase and lipase will be isolated and quantitated by in vitro translation. Once the cellular mechanisms of adaptations are known, the development of these regulatory mechanisms and the effects of perinatal nutrition on this development will be studied.